Neoplasia detection via colonoscopic surveillance among young patients with MSH6 and PMS2-associated Lynch syndrome.
Authors: Alicia Latham, Ying L Liu, Gillain Constantino, Matilde Borio, Cole Poulin, Sean McCoy, Christina Dudzik, Jordan Heiman, Yelena Kemel, Chinedu Ukaegbu, Megha Ranganathan, Madison Parenteau, Sarah R. Kane, Dina Green, Jessica M. Long, Sapna Syngal, Arnold Markowitz, Zsofia Kinga Stadler, Matthew B. Yurgelun, Bryson W Katona
Journal: Journal of Clinical Oncology (2023)

10516 Background: Lynch syndrome (LS) is the most common colorectal cancer (CRC) predisposition syndrome. While patients (pts) with MLH1/ MSH2-associated LS are recommended to start colonoscopy between age 20-25, recent guidelines recommend delaying initiation in pts with MSH6/ PMS2-associated LS to age 30-35. However, data on findings from colonic surveillance in young MSH6/ PMS2-LS pts are limited. Methods: We performed a retrospective review of a multi-institutional cohort of pts with MSH6/ PMS2-associated LS who underwent any colonic surveillance prior to age 50, and assessed corresponding pathology results. Neoplastic lesions were defined as a CRC, adenomas, or non-hyperplastic serrated lesions. Clinicopathologic variables were reported with summary statistics and compared using non-parametric tests at the patient level and among pooled procedures. Results: We identified 285 pts [161(56%) MSH6; 124(44%) PMS2] with history of colonic surveillance prior to age 50. 190 (67%) pts were female, with similar sex distribution among the MSH6 and PMS2 groups. 107 (38%) pts had personal history (hx) of any cancer, 67 (42%) MSH6 and 40 (32%) PMS2, including 58 (20%) with CRC [35(22%) MSH6; 23 (19%) PMS2]. Median age at CRC diagnosis (dx) was 39 and did not differ between groups (41 MSH6 vs. 37 PMS2, p = 0.47) with 16 (5.6%) pts dx prior to age 35. 157 (57%) pts had a family hx of CRC, and there was no difference in the rate of CRC between pts with or without family hx of CRC [50%(n = 25) vs 60%(n = 31), p = 0.33]. Pts underwent a median of 2 colonic surveillance procedures (range 1-12) with 824 total procedures, 806 (98%) colonoscopies and 18 (2%) sigmoidoscopies, with 691 (85%) occurring at an academic/tertiary center. Among the 824 pooled procedures, there were 194 (24%) procedures with neoplastic lesions identified, including 19 (2.3%) with advanced adenomas or advanced serrated lesions and 34 (4.1%) with CRC. Among 247 procedures completed at age &lt; 35, 43 (18%) detected neoplastic lesions, including 4 (1.6%) with advanced adenomas or advanced serrated lesions and 9 (3.6%) with CRCs. Notably, in 123 procedures performed prior to LS diagnosis, 43 (35%) had a neoplastic finding with 28 (23%) showing CRC. These findings did not differ between the MSH6 and PMS2 groups. Conclusions: Among this large, multi-institutional cohort of pts with MSH6/ PMS2-associated LS with history of colonic surveillance performed prior to age 50, colonic neoplasia was found at similar rates in both MSH6 and PMS2-associated LS. 20% of overall pts had CRC, with 48% presenting prior to LS dx. In surveillance procedures performed &lt; age 35, the upper threshold of initiation of colonic surveillance as per NCCN, 18% found a neoplastic finding with 3.6% finding CRC, highlighting the need to optimize the age of colonic surveillance initiation in MSH6/ PMS2-associated LS.